The invention relates to monoclonal antibodies (MAbs) and fragments thereof which bind to defined tumor-associated antigens, principally of small cell lung carcinoma (SCLC), of melanoma, of neuroblastoma and other tumors of neuroectodermal origin, to hybridoma cells for the preparation thereof, and to the antigens which can be defined and/or isolated with the aid of these antibodies or antibody fragments. The antibodies, antibody fragments and antigens can be used as diagnostic aid, active substance or active substance carrier.
The identification, characterization and therapy of tumors is one of the most important areas of diagnosis and therapy. Development in this area has made great advances owing to the possibility of producing monoclonal antibodies of high specificity. Particularly important in this connection has proven to be the identification of so-called tumor markers. By tumor markers are meant products of the tumor cell, for example tumor-associated antigens, but also substances formed by the healthy tissue as reaction of the body to the malignant growth. Examples of known tumor markers are CEA, AFP but also tumor antigens defined by monoclonal antibodies, such as, for example, CA 19-9 or CA 125.
The main area of use of tumor markers in in vitro diagnosis is in the therapy and monitoring the progress of tumor patients. Certain tumor markers can also be employed for differential diagnosis or for screening of risk groups.
A number of tests have already been carried out for the identification of small cell lung carcinoma (SCLC). Thus, for example, it is known that there is increased formation of neuron-specific enolase, an isoenzyme of enolase (EC 4.2.1.11), by malignant tumors of neuroectodermal origin, such as, for example, small cell bronchial carcinoma or neuroblastoma, and increased serum concentrations thereof occur in tumor patients.
However, it has emerged that false negative results are given by some of the patients suffering from the above-mentioned tumors. Furthermore, since red blood cells, but also platelets, contain relatively large amounts of NSE, it is the case that, owing to lysis thereof, falsely raised NSE serum or plasma levels and thus false positive values are measured (Pahlman et al., Tumor Biology 5: 127-139, 1984).
European Patent Application 0,323,802 discloses a monoclonal antibody against a cell surface antigen of lung carcinomas. However, MAIER et al. (Br. J. Cancer, 1989, 59, 692-695) disclose that the antibody SWA 20 used in EP 0,323,802 recognizes an epitope (cluster 5) which showed a moderately to strongly positive reaction only with 45% of tested SCLC samples.
It is therefore desirable to produce another specific tumor marker, which is independent of NSE, for neuroblastoma and small cell lung carcinoma.